The objective of this program is developing new models for biomedical research utilizing the natural genetic variation found in sexually reproducing small research animals. The emphasis has been with certain mutants which are known to affect the functioning of the immune system, metabolic and neurological systems in rats and mice. The strategy has been to establish these mutants on different genetic backgrounds as well as making different combinations of independently appearing mutants. The results has been the formation of a unique resource of animal models which is gradually finding increasing acceptance by the research community.